X-151179756-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004224.3(GPR50):c.188-15C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.86 (29006 hom., 27133 hem., cov: 22)
  • Exomes 𝑓: 0.87 (269006 hom. 269802 hem.)
  • Failed GnomAD Quality Control
• Consequence: GPR50 NM_004224.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

GPR50 (HGNC:4506): (G protein-coupled receptor 50) This gene product belongs to the G-protein coupled receptor 1 family. Even though this protein shares similarity with the melatonin receptors, it does not bind melatonin, however, it inhibits melatonin receptor 1A function through heterodimerization. Polymorphic variants of this gene have been associated with bipolar affective disorder in women. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High Homozygotes in GnomAd at 29009 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR50	NM_004224.3	c.188-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000218316.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR50	ENST00000218316.4	c.188-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004224.3	P1

Frequencies

GnomAD3 genomes AF: 0.859 AC: 94079 AN: 109573 Hom.: 29009 Cov.: 22 AF XY: 0.852 AC XY: 27086 AN XY: 31803

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.824

GnomAD3 exomes AF: 0.829 AC: 118804 AN: 143339 Hom.: 33258 AF XY: 0.841 AC XY: 39418 AN XY: 46845

Gnomad AFR exome AF: 0.896

Gnomad AMR exome AF: 0.625

Gnomad ASJ exome AF: 0.891

Gnomad EAS exome AF: 0.722

Gnomad SAS exome AF: 0.871

Gnomad FIN exome AF: 0.886

Gnomad NFE exome AF: 0.881

Gnomad OTH exome AF: 0.821

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.874 AC: 883325 AN: 1010817 Hom.: 269006 Cov.: 19 AF XY: 0.877 AC XY: 269802 AN XY: 307525

Gnomad4 AFR exome AF: 0.899

Gnomad4 AMR exome AF: 0.631

Gnomad4 ASJ exome AF: 0.889

Gnomad4 EAS exome AF: 0.687

Gnomad4 SAS exome AF: 0.874

Gnomad4 FIN exome AF: 0.883

Gnomad4 NFE exome AF: 0.889

Gnomad4 OTH exome AF: 0.856

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.859 AC: 94117 AN: 109625 Hom.: 29006 Cov.: 22 AF XY: 0.851 AC XY: 27133 AN XY: 31865

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.871

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.823

Alfa AF: 0.864 Hom.: 11382

Bravo AF: 0.846

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.88
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1202874; hg19: chrX-150348228;